Takeshi Shimamura, Zhao Chen, Margaret Soucheray, Julian Carretero, Eiki Kikuchi, Jeremy H Tchaicha, Yandi Gao, Katherine A Cheng, Travis J Cohoon, Jun Qi, Esra Akbay, Alec C Kimmelman, Andrew L Kung, James E Bradner, Kwok-Kin Wong
PURPOSE: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non-small cell lung cancer (NSCLC) with BET inhibition...
November 15, 2013: Clinical Cancer Research